9-[3-(2-hydroxyethylamino)-propylamino]-2-methoxyacridine and method for its production



Patented Nov. 21, 1950 9.13 (2 HYDROXYETHYLAMINO) PRO ,pyr mumogr NIETHOXYACRIDINE'AND METHOD FOR ITS PRODUCTION Alexander R. Surrey, Albany, N. Y., assignor to Sterling-'Drugj-Inm, Wilmington, Del, a corporation of Delaware Noprawing, Application January 22, 1949, Serial No. 72,270

The present invention relates to new chemotherapeutically useful acridine compounds derived from a Q-aminoacridine, and the preparation thereof. More particularly, said acridine compounds are 9 3- 2 -hydroxyethylamino) propylamino)-2-methoxyacridine and acid addition salts thereof.

The compounds of this invention have been found to possess useful chemotherapeutic properties, especially as anthelmintic agents.

The basic acridine compound, 9-(3-(2-hydroxyethylamino)propylamino) 2 methoxyacridine having the formula can be attached stepwise to the acridine nucleus.

In such a process, 9-chloro-2methoxyacridine or 2-methoxy-9-phenoxyacridine hydrochloride is heated with 3-hydroxypropylamine to give 9- (B-hydroxypropylamino) 2 methoxyacridine, which is then treated with a halogenating agent such as thionyl chloride to yield 9-(3-chloropropylamino) 2 methoxyacridine, which, in turn, is treated with 2-hydroxyethylamine to give the desired basic acridine compound, 9-(3- (2 hydroxyethylamino)propylamino) -2-methoxyacridine.

The salts of the instant invention are prepared by treating the foregoing described basic acridine compound with the appropriate acid. In practicing my invention I found it convenient to employ the dihydrochloride salt. However, other salts are within the scope of the invention. Included among other salts which may be employed are the following, formed by reacting the base with the appropriate relatively non-toxic inorganic or organic acid: the dim- -3= Claims. (01. 260279) 2. drobromid'e diphosphate', disulfate; disulfamat'e, diethanesulfonate, ditartrate, dicitrate, disuecinate, diacetate, dibenzoate, dioleate, and. the like.

The following examples will further illustrate specific embodiments of my invention.

EXAMPLES 3 (Z-hydromyethylamino) -propylamine.180 g. of acrylonitrile was added-dropwise with stirring over a period of minutes to 305 g. of 2- hydroxyethylamine, while maintaining the temperature below 30 C. After stirring for five hours the reaction mixture was heated on the steam bath for 30 minutes and then allowed to stand overnight at room temperature. After removal of the excess 2-hydroxyethylamine by distilling in vacuo, the reaction mixture was dissolved in 1.1 liter of ammoniacal ethanol (approx. 12%) and reduced with Raney nickel at C., the initial hydrogen pressure being about 1300 pounds. The product, 3-(2-hydroxyethylamino)propylamine, was distilled at 105-114" C. at 1 mm.; 11 1.4845; yield 280 g.

9 (3 (Z-hydroxyethylamino)propylamino)- Z-methoscyacridine dihydrochZoride.A stirred mixture of g. of phenol and 36 g. of 9-chloro- 2-methoxyacridine was heated on the steam bath for about 15 minutes and 21.5 g. of 3-(2-hydroxyethylamino)propylamine was added. After heating for about 2 hours on the steam bath the slightly cooled reaction mixture was poured into a stirred solution of 37 cc. of concentrated hydrochloric acid in 600 cc. of acetone. After about 1 hour the product was filtered off, washed with acetone and then freed from most of the adhering phenol by stirring in hot acetone and filtering the mixture while hot. The resulting solid was recrystallized twice from ethanolwater, yielding the desired product, 9-(3-(2-hydroxyethylamino)propylamino) 2 methoxyacridine dihydrochloride, M. P. 213.8-215.8 C. (corn).

I claim:

1. A compound selected from the group consisting of 9 (3 (2-hydroxyethylamino)propylamino) -2-methoxyacridinehaving the formula NHCHzCHzCHzNHCHzOHzOH CHaO and acid addition salts thereof.

2. 9- (3- (Q-hydrdfithylamino) propylamino) 2-methoxyacridine dihydrochloride having the formula NHCHzOHzCHzNHCHzCHzOH-ZHCI CHzO 3. In the process of preparing 9-(3-(2-hy- 10 Number droxyethylamino)propy1amino) 2 methoxyacridine having the formula NHOHzOHzCHzNHCHzCl-IBOH the step which comprises heating a member of the group consisting of 9-ch1oro-2-methoxyacridine and 2-methoxy-9-phenoxyacridine hy- The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Mietzsch et a1 Apr. 5, 1938 OTHER REFERENCES Shriner et a1.: Synthetic Antimalarials (published in Bloomington, Ind. 1941), page 30.

Mosher: Antimaiarials: Natural and Synthetic (Edwards Bros. Ann Arbor, Mich. 1942), page 69.

Chem. Abst., v01. 37, page 2408 (1943) citing:

20 Proc. Soc. Exptl Biol. Med. vol. 52. pp. 90-91 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 9 - (3 - (2-HYDROXYETHYLAMINO) PROPYLAMINO) -2-METHOXYACRIDINE HAVING THE FORMULA 